Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma

TL;DR

A marine compound called plitidepsin combined with dexamethasone shows similar survival and better safety compared to a standard treatment in patients with advanced multiple myeloma.

Contribution

A novel matched comparison of plitidepsin plus dexamethasone versus pomalidomide plus dexamethasone in relapsed/refractory multiple myeloma using real-world data.

Findings

Plitidepsin plus dexamethasone was non-inferior to pomalidomide plus dexamethasone in median overall survival.

Plitidepsin plus dexamethasone had fewer severe hematological side effects and infections.

The safety profile of plitidepsin plus dexamethasone included more gastrointestinal issues and muscle-related adverse events.

Abstract

Plitidepsin (P) is a marine-derived anticancer compound isolated from the tunicate Aplidium albicans. P plus low-dose dexamethasone (LD-DXM) was evaluated versus LD-DXM alone in patients with relapsed/refractory multiple myeloma (r/r MM) in the randomized phase III ADMYRE trial. In absence of a randomized study with P + LD-DXM vs. POM + LD-DXM, a direct matched comparison between P + LD-DXM (ADMYRE data) and pomalidomide (POM) + LD-DXM as an External Control Arm (ECA) was conducted using individual patient-level data from several contemporary POM + LD-DXM trials with a similar design. A first analysis (ECA1) showed that P + LD-DXM was non-inferior to POM + LD-DXM in terms of median overall survival (OS): 11.8 vs. 13.9 months; HR = 1.009 (95%CI, 0.812–1.254; p = 0.9336). Safety profile showed a lower rate of grade ≥ 3 hematological treatment-related adverse events (TRAEs) (neutropenia 2.5% vs. 37.1%; thrombocytopenia 2.5% vs. 13.2%) and infections (8.1% vs. 18.7%) for P + LD-DXM, and a higher rate of grade ≥ 1 gastrointestinal TRAEs (52.8% vs. 27.4%), grade ≥ 3 blood creatine phosphokinase (14.3% vs. 0%) and grade ≥ 3 myalgia (5.6% vs. 0%). A second analysis (ECA2) compared POM + LD-DXM with the LD-DXM alone arm included in ADMYRE and showed a treatment effect in OS (HR = 0.762; 95%CI, 0.566–1.026) similar to that observed in ADMYRE (HR = 0.797, 95%CI, 0.596–1.067). Safety profile of POM + LD-DXM was associated to a higher rate of TRAEs, as expected for a combination. In conclusion, P + LD-DXM can be an alternative therapeutic option in r/r MM as this comparison shows that P + LD-DXM is non-inferior in OS to POM + LD-DXM with an advantageous safety profile in terms of hematological and infection events.

The online version contains supplementary material available at 10.1007/s00277-026-06811-w.

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